In the proposed research project, candidate TaO nanoparticle contrast agents for computed tomography (CT) will be developed with desired physical and biological properties for clinical use. We have developed a first-in-class zwitterioni tantalum oxide (TaO) nanoparticle CT contrast agent, specifically designed for contrast-enhanced CT imaging of large-to-obese patients. These nanoparticles have near-ideal physicochemical properties for clinical formulation and have shown equivalent biological performance (organ retention and acute tolerability) in rat dosing studies. We anticipate at least 50% radiation dose reduction when imaging this patient population, while producing image quality that is equivalent or better than what is provided with commercially-avail- able iodinated contrast agents. Aim 1. Develop tantalum oxide nanoparticles that are safe and practical for eventual clinical use -Building upon our previous foundational research, we will develop new zwitterionic TaO nanoparticles by modifying particle size and shell chemistry to benefit CT imaging performance. We will demonstrate that the nanoparticles are biologically safe and have organ retention that is comparable to iodine-based counterparts. Aim 2. Determine tantalum-specific CT imaging protocols to optimize image quality at reduced radiation dose for the large-to-obese patient population.-We will identify tantalum-specific CT acquisition protocols to provide equivalent or improved image quality (better signal-to-noise ratio, reduced artifacts) at 50% reduced radiation dose, when compared to iodine-based counterparts. We will perform computer simulations and phantom experiments using both simple and anatomically-relevant anthropomorphic phantoms, which represent a wide range of patient sizes. Aim 3. Demonstrate improved imaging safety without loss of diagnostic performance in a porcine animal model that is representative of the large-to-obese patient population. -We will demonstrate contrast dose and/or radiation dose reduction (improved imaging safety) using a porcine animal model mimicking large-to-obese patients. We will characterize diagnostic performance, using metrics that are a function of the imaging signal-to-noise ratio.